by Vittorio Bollo

Lyra Maskie at 150

It’s 2144 and Lyra Maskie is celebrating her 150^th birthday. Born in 1994, Lyra’s life has spanned three different centuries and much has changed since she was a little girl at the conclusion of the 20^th century. She often cannot believe just how much has changed during her lifetime. These immense paradigm changes have included everything from the energy used to power cities and homes to how people get around, not to mention what and how they eat. Even the very nature of work has changed due to the demise of the concept of ‘work’ as we know it, thanks to the ‘Age of AI’ and allied measures such as UBI.

But perhaps nothing has changed society, not to mention Lyra’s entire life, more than the fact that people are living far longer in the 22^nd century. This enormous paradigm change regarding longevity was already well in progress by the latter part of the 21^st century. Lyra remembers her grandfather, a geneticist, regaling her with stories about the fantastic changes in longevity studies that he had witnessed and been a part of, changes which had seemed akin to pure science fiction just a few decades earlier.

Her father and aunt had been so inspired by his stories that they had ventured into the same field, becoming what would be termed ‘lifers’. What was once a word used to describe people who were jailed for the entirety of their life, would transform into the nickname for those who studied how to ensure that people lived longer lives. Lyra has always been proud of her family’s contribution to longevity, if only because of how much it had transformed human society. Some of the changes had come in jolts, of course, but most of the changes had been gradual, as these things often are. Her aunt would often refer to the longevity revolution as “the quietest revolution the world has ever seen”.

‘Oh, I must get ready!’ Lyra thought to herself. Family and friends were throwing her a party and she was running late. Nothing too big or fancy, mind you, since 150 was no big deal. ‘150 is the new 100,’ so the cliche went. Lyra had heard the same thing when turning 140. Millions of people had reached 150 like her, and just the other day Lyra had heard about a lady in France who had celebrated her 174^th birthday and was still going strong (‘Why is it always the French that live the longest?’ Lyra wondered). Now scientists were predicting further breakthroughs that would allow people to live to the ripe old age of…well, Lyra simply couldn’t imagine living that long!

The concept of people living as long as 150 years or more is less science fiction today than it was even a generation ago. Advances, specifically in gene therapy and allied evolving technologies, mean that we can now better speculate on and envisage what the future of longevity might entail. This article will explore some of those scientific developments, as recent as they are exciting.

The Science of Longevity

For now at least, gene therapy, which includes what is known as ‘gene editing’ in its different forms, is leading the way in studies regarding longevity. The focus is on the ability to replace or repair so-called ‘faulty genes,’ since it is at the genetic level that cellular degradation occurs which leads to the inevitable deterioration of organs and tissue within the body. This in turn leads to disease and the aging process itself. aging at the cellular level is what drives aging in us all, however that aging manifests itself. Genes are the possible lock that are the key to slowing down the aging process.

CRISPR

Gene editing has been around for some time. 1987 saw the emergence of what is known as CRISPR, which stands for Clustered Regulatory Interspaced Short Palindromic Repeats. By extension, CRISPR-Cas9 is a process that uses molecular blades to make incisions to the Cas9 endonuclease in host DNA, thereby allowing the removal of unwanted genes and the addition of new genes. Geneticists such as Jennifer Doudna and Emmanuelle Charpentier were able to re-engineer RNA molecules and Cas9 into a two-component system that is more easily manipulated and programmed to target any DNA sequence.

Jennifer Doudna describes CRISPR-Cas9 as being the DNA version of the cut and paste function one associates with a text document. A snip here and a snip there, and genetic material can effectively be re-engineered. This is important if one considers that DNA is the ‘memory program’ of any human cell (or cell of any any living entity, for that matter). By re-engineering DNA itself, one can literally tap into the endless possibilities of ‘cell memory’ itself. And one of those memory banks is the degradation and slow death hot-wired into any living cell.

Longevity essentially requires the re-wiring of living cells as we know them. Geneticists (also referred to rather hilariously as ‘genomic mechanics’) are at the forefront of this challenge.

Some noteworthy developments regarding CRISPR-Cas9 gene therapy include:

• Unlike many medical technologies and therapies, the CRISPR-Cas9 therapy is actually quite affordable and relatively easy to use. It is one of the reasons why the gene therapy had such swift uptake among researchers. Like uncomplicated software, the relative simplicity of CRISPR technology means that it is highly versatile and easily adaptable by researchers.
• In 2016, Scientific American reported how the CRISPR-Cas9 gene editing tool had effectively been used by a team at the University of Pennsylvania and the Children’s Hospital of Philadelphia (CHOP) to treat sickle cell disease, a hereditary blood disorder, in mice.
• In 2019, the CRISPR-Cas9 gene therapy was successfully used to cure sickle-cell disease in a human patient. Victoria Gray was the patient and the first person in the US to receive the landmark treatment in a trial at the Sarah Cannon Research Institute in Nashville, Tennessee. Within four months of the therapy, Gray’s blood tests showed that 94.7% of her red blood cells contained the edited protein. This far exceeded her medical team’s expectations.
• 2019 was also the year when a series of human test studies utilizing CRISPR-Cas9 were rolled out worldwide, including in Canada and Europe, for a range of different cancers including myeloma and sarcoma, and even a an inherited form of blindness known as Leber congenital amaurosis. Fyodor Urnov, a gene-editing scientist at the Altius Institute for Biomedical Sciences in Seattle and the University of California, Berkeley, would refer to 2019 as the year when “the training wheels” would finally come off CRISPR-Cas9 so that its true, positive potential could be explored.

Gene editing is not without its controversies, of course. The potential social and ethical scourge of ‘designer babies’ and a ‘genetic divide’ between the genetic ‘haves and have-nots’ are constantly trumpeted as reasons why some call for greater controls or even a moratorium on most forms of gene therapy. The scientific world was shocked, even outraged, when a Chinese researcher, He Jiankui of the Southern University of Science and Technology in Shenzhen, China, revealed in late 2018 that he had successfully created “modified designer babies” using the CRISPR gene therapy tool.

However, one thing is certain: if a Lyra Maskie is to indeed celebrate her 150^th birthday in 2135, then such opposition to gene therapy will need to have been addressed and, ultimately, swept aside.

Nature Calling

Scientists are also increasingly turning to nature itself to try and unravel some of the secrets of longevity in other species on Earth. In that vein, The Starset Society has already written on biomimicry . If our ability to improve our architecture or technology by mimicking nature has been proven, then why should medicine be any different?

Take the bowhead whale, for example, which is second only to the blue whale as the largest mammal on Earth. They are renowned for their longevity: according to Inuit folklore, they can live the “equivalent of two human lifetimes”. Bowhead whales have been known to live to 150 years, and some even as long as 210 years, it is now believed. Scientists have marvelled at how these magnificent giants show remarkably few ill-effects after so many years living in the wild and exposed to the harsh oceanic elements.

One such scientist is João Pedro de Magalhães at the University of Liverpool in England, who believes that these whales must be somehow naturally protected from age-related disease and deterioration. Bowhead whales buck the trend regarding one important constant in the animal kingdom, namely, the larger the animal, the more prone it is to tumors. Yet bowhead whales don’t suffer from cancers, even with lifespans of up to two centuries. As de Magalhaes suggests: “When put in the context of other animals, [these whales] really are outliers. They must have tumour-suppressing mechanisms that we lack.”

At the other end of the spectrum regarding longevity in the animal kingdom is this maxim: the smaller the animal, the shorter its lifespan typically is. However, the naked mole rat lives to 30 years, far beyond the average lifespan of nearly all other rodents. Furthermore, they seem highly resistant to cancers, with not one case of cancer being found among thousands of those studied to date. This may be due to the fact that the cells of naked mole rats tend to stop growing when they become too dense, which is usually how tumors arise and spread in organisms. This is thanks to a version of a chemical known as hyaluronan.

An even more extreme example of the too-small-to-live-long hypothesis is that of Brandt’s bat, which lives to more than 40 years yet is the size of a sugar cube! Scientists such as Vadim Gladyshev at Harvard University have found that these tiny bats have unusual mutations around their receptors for growth hormone and insulin-like growth factor. These mutations may offer clues regarding how metabolism can be controlled in humans. That could be hugely important given that cellular degradation due to metabolic shifts in the body is a leading factor in the aging process.

Is 1000 Years Old Really Possible?

If Lyra Maskie in the 22^nd century celebrating her 150^th birthday as being ‘nothing that special’ seems remarkable, then what of possibly living to beyond 1000? A famous proponent of this mind-blowing theory is Aubrey de Grey (full name: David Nicholas Jasper de Grey), a Cambridge-educated English author and biomedical gerontologist, who is the Chief Science Officer of the SENS Research Foundation and VP of New Technology Discovery at AgeX Therapeutics. It was de Grey that made the startling observation that there are already people living today who could live to be a 1000 years old. The only obstacle in the way of this enormous longevity is what de Grey refers to as the “pro-aging trance” due to an orthodox, fatalistic acceptance of aging by many in today’s society and scientific community.

de Grey and others are adamant that the body’s aging process could be effectively slowed down to a crawl due to a series of scientific-medical interventions and processes, some of which could include:

• iPS, or induced pluripotent stem cells – these cells can potentially be used to create any cell or tissue the body needed in the treatment of a wide range of diseases, from diabetes to heart disease, as well as injuries such as spinal cord injury. This is what has been popularly referred to as stem cell therapy, itself fraught with controversy for years now, including the ethical use thereof;
• the use of AI in the early detection, improved diagnosis, and more individualized treatment of diseases and adverse health effects;
• nanobots (or nanomedibots), which can be released into the bloodstream and programmed to search out and destroy harmful viruses and cancers within a person’s body;
• smart health monitors – examples of ‘wearable tech’ that will become increasingly mobile, inexpensive, and geared to an individual’s unique health status and conditions;
• brain stimulators, such as deep brain stimulation, which involves implanting electrodes within certain areas of your brain. These produce electrical impulses that regulate abnormal impulses, as well as chemicals, within the brain. According to the Mayo Clinic, brain stimulators are already being used or being considered for use in many conditions, including:
  • epilepsy
  • Parkinson’s disease
  • dementia
  • Huntington’s disease
  • multiple sclerosis
• replacement organs grown in the laboratory or in donor animals

Or Is 125 As Good As It Gets?

There are those scientists, however, who critique the idea of living into the hundreds or even to 1000. These skeptics cite a 2016 study by researchers from the Albert Einstein College of Medicine in New York, as reported in the Nature journal. According to the study, exhaustive statistical analysis of countries with the largest number of “super-centenarians,” i.e. those aged 110 or more, found that the average age at death for this group had not increased since 1968 and that living beyond 125 was not feasible for the human body.

According to Jan Vijg, one of the co-authors of the 2016 study, one conclusion was that we had reached the peak of longevity for the first time in human history – and that peak was no more than 125 years. Vijg further commented that, whilst longevity had increased dramatically in the past few decades for those over the age of 70, this had not been the case for those over 100. Still today, very few are able to live beyond a century, he contended.

There were also questions put forward by the researchers regarding other issues related to longer lifespans, including quality of life and that question often posed by those who argue against dramatic increases in longevity: Do people really want to live that much longer?

However, the 2016 study by the Albert Einstein College of Medicine team of researchers has two fundamental flaws: Firstly, until very recently the longevity of people who lived well above 100 years could only be benchmarked against prevailing medical standards. And, once genetic editing and other anti-aging technologies really come to the fore, the medical practices we had until now will seem primitive in comparison. We simply cannot be certain that people will not live beyond 125 years with these breakthrough technologies.

Secondly, the study cannot factor just how revolutionary a single medical breakthrough can be in terms of longevity. The discovery of penicillin and subsequent availability of antibiotics is an excellent example of this. It is not a quantum leap to deduct that something akin to, say, CRISPR or nanobots could be the penicillin of the 21^st or 22^nd centuries or beyond.

Long Live Longevity

The naysayers regarding our increased longevity remain plentiful but there are those who are highly optimistic about the future of longevity. Tom Kirkwood, Associate Dean for aging at Newcastle University in England, believes that the ‘ceiling’ on the lifespan of humans should continue to rise if only because the aging process itself is highly malleable and, thus, open to ‘tweaks’ and improvements due to innovative technologies and therapies.

There is also another compelling argument for the belief in future improved longevity: we continue to know relatively little about the human aging process. We understand how aging occurs due to deterioration at the genetic and cellular levels, but we still don’t understand why that is. João Pedro de Magalhães is of the opinion that aging is the greatest direct cause of suffering and death in the modern world. He believes that If we could retard aging even a little bit, the benefits to humanity would be unprecedented.

And perhaps that belief by João Pedro de Magalhães is key to the entire thesis on why we can seriously consider a (near) future world of dramatically increased longevity: all it might take is a small genetic shift here and a minor scientific side-step there. Perhaps we won’t need a huge leap of scientific ability, not to mention scientific faith, in order to allow people to live far longer lives. As Cynthia Kenyon, Vice President of aging research at Google’s longevity-focused Calico Labs, noted recently: “No one, particularly not evolutionary theorists, predicted that single-gene mutations could slow the aging process and double the lifespans of animals. But they can.”

Someone like Lyra Maskie certainly won’t be that concerned about all these arguments on her 150^th birthday. She will be too busy preparing for an even longer life, much as someone will do so today at half her age. Our expectations about our lifespans have already changed so dramatically in just the last few years, why should it be any different for someone alive in 2135? There is a good chance their expectations of longevity will be far greater than ours.

As Lyra’s father always liked to quip, “Longevity sure has come a long way”. By the 22^nd century, Lyra knew that it sure had. And today we should accept that it almost surely will.